The role of TASK-3 potassium channels in theta oscillations and behaviour

Abstract

The two pore-domain potassium channel TASK-3 provides a potassium leak conductance in the mammalian brain and is activated by volatile anaesthetics. Previous studies have shown that TASK-3 knockout (KO) mice have a number of physiological and behavioural abnormalities. In particular, TASK-3 KO mice lack the type-2 theta oscillation (4-8 Hz) usually present in the electroencephalogram (EEG) under halothane anaesthesia, while the higher frequency type-1 theta oscillation (8-12 Hz) recorded during exploratory behaviour is unaffected. That TASK-3 KO mice also have moderate memory impairments, led us to ask whether there might be a link between type-2 theta deficits and impaired mnemonic behaviour. Our results indicate that TASK-3 KO mice also have impaired type-2 theta oscillations during freezing behaviour in a predator exposure test, suggesting possible sensorimotor integration problems. TASK-3 KO mice were found to have a mild impairment in working memory in the T-maze, but object recognition and emotional memory were intact, excluding a role for the TASK-3-dependent theta oscillation in these processes. Further studies then sought to understand the mechanistic role of TASK-3 in the theta oscillation using recombinant Adeno-associated viruses (rAAVs). We first investigated a possible functional role for the type-2 theta oscillation in mediating anaesthesia, and then confirmed that the halothane-associated theta oscillation was dependent upon cholinergic input from the medial septum to the hippocampus. TASK-3 was then re-expressed via rAAV in the medial septum in KO mice, resulting in partial rescue of the type-2 theta oscillation. Our results show that (1) the type-2 theta oscillation plays a redundant role in halothane anaesthesia, (2) type-2 theta deficits in TASK-3 KO mice have minimal effect on memory processing, and (3) that TASK-3 channels in the medial septum play a facilitatory role in type-2 theta oscillations.